A major objective of this proposal is the study of fatty acid transport from adipose tissue and other host tissue lipids directly to cancer cells by pathways which do not involve plasma free fatty acids (FFA) as intermediates. We also plan to elucidate the metabolic controls by which such direct transport may be effected (e.g., neoplastic hormones or other agents which may induce local lipolysis and the release of FFA into interstitual fluids). Other broad objectives are (1) to use radioisotopic tracer techniques and multicompartmental analyses to estimate rates of lipid metabolism and transport into and out of cancer cells in vivo under varying physiological conditions; (2) to define the pathways involved in the conversion of dietary lipids to the metabolic economy of the cancer cell; (3) to investigate lipogenic activation by dietary carbohydrate in cancers of mice fed fat-free, high carbohydrate diets; and (4) to alter the lipid composition of tumor cell membranes by strategies derived from the above information. The information derived from these fundamental studies of lipid metabolism in neoplastic disease is to be used as the basis of another project which is designed to elucidate whether alteration of cancer cell membrane lipid composition will render the cells selectively susceptible to anti-cancer agents.